The influence of age on CD4 helper activity. The efficacy of vaccines for highly contagious infections, such as influenza, are greatly decreased in the elderly. This is extremely important since elderly persons exhibit a much increased risk of hospitalization and death from influenza compared to younger persons. Numerous studies have attempted to address this issue by examining the function of aged T cells. The drawback of these previous studies is that they employed heterogeneous populations of T cells from aged mice which are quite different from T cell populations found in young mice. This makes interpretation of these experiments difficult, since age may affect many aspects of the total T cell population. In fact, it is highly likely that there are dramatically different numbers of antigen-specific CD4 cells in young and aged populations. This may also account for the differences that have been observed in young and aged helper function. Aged mice have been shown to exhibit decreased GC formation and reduced antibody affinity maturation upon immunization. The goal of this application is to use a TCR Tg model to determine what aspects of aged CD4 function contribute to decreased B cell helper activity. This will allow us to directly compare the cognate helper activity of homogeneous populations of Tg CD4 cells from young and aged mice. In this model, naive Tg CD4 cells from aged mice produce less IL-2 upon TCR stimulation compared to young cells. Decreased IL-2 production leads to reduced expansion and subsequent effector generation, as well as reduced CD4OL expression. If we can determine the mechanism of decreased GC formation and subsequent reduction in antibody titers in the aged, we can then begin to examine methods for improvement and, ultimately, increase the efficacy of vaccination in the aged.